1. Field of the Invention
Peritoneal dialysis can be used for treatment of both acute and chronic renal failure. The treatment should ideally serve to restore the composition of the blood of the patient to that which would prevail if the patient's kidneys were functioning normally, and to maintain the blood in such a state. In the present state of the art, such ideal results are not achievable and are probably not likely to be achieved in the near future, especially as some of the normal kidney functions, for example synthesis of hormones and enzymes, are of such a nature that dialysis of any kind cannot be expected to compensate for loss of these functions. However, even with its recognized imperfections, the established technique of carrying out peritoneal dialysis using dextrose as the osmotic agent has been of great value, and any improvement over it is of potential importance.
Peritoneal dialysis is an alternative to haemodialysis. In haemodialysis, the patient's blood is treated outside the patient's body to effect removal of water and waste products, such as urea and creatinine, by subjecting the blood to a process of dialysis in an artificial kidney machine. In peritoneal dialysis the patient's blood is not withdrawn from the body; instead, a dialysing solution is introduced into the abdominal cavity and removal of water and waste products is effected by dialysis across the peritoneal membrane.
In order to create the osmotic pressure which is necessary to cause peritoneal dialysis, the dialysing solution must contain an osmotic agent which has, in the past, normally been dextrose.
It has been recognized for some time that the use of dextrose as the osmotic agent is not entirely satisfactory, mainly because the dextrose can pass from the abdominal cavity through the peritoneal membrane, causing an undesirably rapid drop in the osmotic pressure, so that the dialysing solution has to be removed and replaced by fresh solution more frequently than is desirable, and also causing an increase in the level of dextrose in the blood, which is often injurious to the patient.
2. Background Art
It has previously been suggested that the performance of peritoneal dialysis solutions might be improved if dextrose were replaced, as the osmotic agent, by a mixture of glucose polymers. One such suggestion appears to have been at a seminar on renal disease at Manchester Royal Infirmary on July 1st, 1981. Subsequently, P.C.T./U.S. Specification No. 82/00774 disclosed a peritoneal dialysis solution comprising a water solution of physiologically tolerable pH, having physiological salts and metabolizable carbohydrate polymers having an average degree of polymerisation (D. P.) of at least 4 in concentrations sufficient safely to effect the removal of solutes and water from a patient by peritoneal dialysis. The polymers may be glucose polymers having an average D.P. of 4 to 10.
U. S. Pat. No. 3,783,100, Larson et al, January 1, 1974
This patent discloses the preparation of high D.E. conversion syrups which are readily filterable and recoverable. Starch is hydrolyzed under superatmospheric conditions and heated to a temperature of at least 250.degree. F. The hydrolyzate is then cooled to a temperature between 185.degree. F. and 200.degree. F. Alpha amylase still continues to break down the hydrolyzate. The resulting product has a D.E. value greater than 5.
U.S. Pat. No. 3,912,590, Slott et al, October 14, 1975
This patent discloses a process for liquefying and thinning starch by treating an aqueous suspension of at least 25 wt. % starch with alpha amylase produced by B. licheniformis at a temperature from 100.degree.-115.degree. C.
U.S. Pat. No. 3,928,135, Milner, December 23, 1975
This patent relates to preparations of glucose polymers intended for intravenous injection. As stated in this patent at col. 4, lines 22-30, "The invention also includes the novel glucose polymers that are suitable for intravenous use which comprise a mixture of polymers each of which is substantially no more than 10 glucose units long. The difference between this intravenous product and the oral product is that the oral product also contains a proportion, e.g., 10% by weight, of polymers more than 10 glucose units long, and may have present an unspecified number of 1-6 linked units."
U.S. Pat. No. 4,182,756, Ramsey et al, January 8, 1980
This patent relates to the use of glucose polymers having a D.P. ranging from 4-10. Such compositions are used for intravenous administration to human patients.
U.S. Pat. No. 4,239,041, Popovich et al, December 16, 1980
This patent discloses a process and apparatus for continuous ambulatory peritoneal dialysis. Dialysis fluid is passed from a bag through a tube which extends through a surgically implanted dacron cuff and into the peritioneal cavity. The used dialysis fluid is collected in another bag connected by another tube to a coupling next to the dacron cuff.
U.S. Pat. No. 4,339,433, Kartinos et al, July 13, 1982
This patent discloses a peritoneal dialysis solution containing osmolarity increasing agents other than dextrose. Such materials include ethylene maleic acid copolymer resins, carboxymethyl-polysaccharides, carboxymethylpolyvinyl alcohol, polypeptides, proteins, esters of polyvinyl alcohol, polypeptide and carboxylic acid reaction products, hydroxypolycarboxylic acids, polymethylvinyl ether-maleic acid, amino acid and dicarboxylic acid halide reaction products, and predominantly sodium salts of dextran sulfate.
European Patent Application No. 76,355, Ramsey, April 13, 1983
This application discloses a peritoneal dialysis solution comprising glucose polymer, sodium, calcium, magnesium, chloride, lactate, and sodium hydroxide. The average degree of polymerization of the glucose polymer is preferably at least 4, but preferably at least 99% of the glucose polymer molecules should have less than 26 glucose units.
WIPO Application No. WO82/03329, Silk et al, October 14, 1982
This application discloses a glucose polymer preparation consisting predominantly of glucose polymers with a degree of polymerization from 10 to 40. This preparation has a reduced osmotic pressure. The polymers are linked by 1-4 alpha and 1-6 alpha-D-glycosidic chemical bonds.
UK Pat. No. 1,280,001, Hayashibara Co., July 5, 1972
This patent discloses a process for preparing amylitol by treating amylopectin with alpha-1, 6-glucosidase to form amylose, dissolving the amylose in water, adding a nickel catalyst to the amylose solution, and then introducing hydrogen at a temperature not more than 100.degree. C. and a pressure up to 100 kg/cm.sup.2.
UK Patent No. 1,595,596, Takeda Chemical Industries, Ltd., August 12, 1981
This patent discloses bacterial Beta-1,2-glucans produced by bacteria of the genus Alcaligenes and of the genus Agrobacterium. These glucans have an average degree of polymerization of 170. Hydrolyzates and carboxymethylated derivatives of these glucans are also disclosed. These glucans and their derivatives are used in the treatment of mammalian tumors.
J. Rubin et al, "Substitution of a Starch Polymer for Glucose in Peritoneal Dialysis," Nephron, Vol. 39, pp. 40-46 (1985). This article discusses the use in dogs of peritoneal dialysis polymer solutions of maltose and maltotriose, maltotetrose, and maltopentose, in comparison with glucose. The polymers, as shown in Table III of the article, have molecular weights ranges from 319 to 838. The use of these polymers in solution has not shown a clear advantage over the previously used glucose (Gl) solutions.
J. F. Winchester, M.D., et al, "A Comparison of Glucose Polymer and Dextrose as Osmotic Agents in CAPD," Frontiers in Peritoneal Dialysis, John F. Maher, M.D., and James F. Winchester, M.D., Editors, Field, Rich and Associates, Inc., New York (February 1986). This article compares peritoneal dialysis solutions of glucose polymers with solutions of dextrose in CAPD. The glucose polymers have an average molecular weight of 710 and a degree of polymerization from 2 to 15. The discussion of the comparisons show that similar results were obtained regarding the clearance of impurities from the blood between the glucose polymer and dextrose solutions. The article does suggest that combining glucose oligosaccharides of higher molecular weights, along with other osmotic agents such as amino acids, may be a useful alternative to dextrose for use in CAPD solutions.
U.S. Patent Application No. 4,308,255, Raj et al, December 29, 1981
This patent discloses a balanced oncotic pressure fluid suitable as a dialysate in the treatment of patients suffering from loss of kidney function. The solution comprises about 224 mEq sodium, about 164 mEq chloride, about 72 mEq acetate, about 2 mEq potassium, about 3 mEq calcium, about 2 mEq magnesium, about 6% dextran, about 2% dextrose and about 71 mg zinc gluconate. The ratio of sodium to choride in this solution is about 1.37:1.
Jon Gjessing, "The Use of Dextran as a Dialysing Fluid in Peritoneal Dialysis", Acta med. scand. Vol. 185, pp. 237-239, 1969. This article discloses use of a 6% dextran solution (Macrodex) in saline dialysis fluid for peritoneal dialysis. The molecular weight of dextran is 60,000 and the dialysis solution contains no buffers, such as lactate or bicarbonate. On page 239 of the publication, it is stated that the clinical use of dextran solutions for dialysis is principally for patients with diabetes, without oedema or acidosis; and that a dialysing fluid containing dextran, sorbitol, electrolytes, and a small quantity of glucose might prove to be more satisfactory than fluids containing dextran or glucose alone.
UK Patent Application No. 2,042,547A, Verwaerde et al, September 24, 1980
This patent application discloses a starch hydrolysate, optionally hydrogenated, whose glucid spectrum displays:
a content of monosaccharides (DP=1) less than 14%; PA0 a content of disaccharides (DP=2) less than 35%, and preferably less than 20%; PA0 a content of oligosaccharides of DP 4 to DP 10 ranging from 42% to 70%, and preferably from 42% to 60%, the oligosaccharides of DP 5 to DP 7 representing a proportion preferably higher than 25% and more preferably higher than 30%; PA0 a content of polysaccharides of DP higher than 10 less than 32%, and preferably less than 25%. PA0 in the preparation of binders for foundry moulds and cores; PA0 in human feeding, notably the manufacture of jams, chocolates, sausages, ice-creams, chewing-gums and hard candies, the foodstuffs in question being moreover non-cariogenic when the starch hydrolysates used are hydrogenated and their content of products of DP higher than 20 is less than 3%; PA0 in infant dietetics, and feeding of medical patients; PA0 in the preparation of polyurethanes PA0 in the make-up of blood plasma substitutes; and PA0 in the manufacture of dialysis solutions for the treatment of renal diseases.
On page 2, lines 54-68, the starch hydrolysates find use in different fields, including the following: